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Our research focuses on (1) imaging characteristics of Idiopathic Generalised Epilepsies, and (2) how brain inflammation contributes to co-morbidities (depression) and the development of epilepsy, ie epileptogenesis, and epilepsy-associated conditions, in particular primary brain tumours.
Imaging Idiopathic Generalised Epilepsies
Initially funded by the Wellcome Trust, and with support from the Deutsche Forschungsgemeinschaft and the Henry Smith Foundation, we applied advanced fMRI paradigms to define imaging endophenotypes in siblings of patients with Juvenile Myoclonic Epilepsy (JME) and Juvenile Absence Epilepsy.
Figure legend: Comparisons of cortical thickness, surface area, and local gyrification index. Comparisons between JME patients and healthy controls show syndrome-related effects and comparisons between drug-resistant and drug-responsive JME patients characterise effects related to disease severity.
Recently, in collaboration with Dr Bernardo Pimentel, Georgi Kuchukhidze and Eugen Trinka (Paracelsus Medical University, Centre for Neuroscience Salzburg, Austria), we identified (i) a developmental phenotype in individuals with drug-resistant JME, supporting a neurodevelopmental basis for drug resistance and cognitive impairment in JME, and (ii) the structural underpinning to the high efficacy of Sodium Valproate, which appears to be a key modulator of cortical morphology in JME.
Figure legend: We demonstrated a dose-dependent effect of Valproate on the thinning of the cortical motor regions implicated in the pathophysiology of juvenile myoclonic epilepsy, which were not seen in temporal lobe epilepsy.
Imaging blood-brain-barrier integrity and inflammation
In collaboration with Professor Geoff Parker (UCL CMIC) and Professor Alon Friedman (Dalhousie University, Halifax, CA), we employ novel imaging techniques to visualise blood-brain-barrier (BBB) leakage as a marker of neuro-inflammation, including Dynamic Contrast Enhanced (DCE)-MRI and Filter-exchange imaging (FEXI). We combine these methods with structural MRI analysis to study the effects of BBB dysfunction on cortical architecture. We aim to develop brain imaging measures that ultimately help to discover novel treatment approaches for these conditions.
Figure legend: DCE-MRI demonstrating percentage of temporal lobe epilepsy patients with abnormal BBB leakage rate per brain region. Depressed TLE patients showed a trend of more extensive leakage indicative of higher disease burden.
Epilepsy caused by brain tumours
We collaborate with the Barts Health Neuro-oncology Service and Barts Health/QMUL Brain Tumour Research Centre (Anam Anzak, Professor Silvia Marino) to characterise brain structural changes in glioma-associated epilepsy.
Figure legend: Cortical thickness changes in individuals with glioblastoma, with and without lesion-related epilepsy. There is increased cortical thickness in the cortex ipsilateral to the tumour in those with epilepsy, compared to those without seizures. The volume of glioblastomas was also larger in those without epilepsy.
Selected Recent Publications:
- Caciagli L, Ratcliffe C, Xiao F, van Graan LA, Trimmel K, Vollmar C, Centeno M, Duncan JS, Thompson PJ, Baxendale S, Koepp MJ, Wandschneider B. Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings. Epilepsia. 2023 Oct;64(10):2792-2805. doi: 10.1111/epi.17719.
- Cafri N, Mirloo S, Zarhin D, Kamintsky L, Serlin Y, Alhadeed L, Goldberg I, Maclean MA, Whatley B, Urman I, Doherty CP, Greene C, Behan C, Brennan D, Campbell M, Bowen C, Ben-Arie G, Shelef I, Wandschneider B, Koepp M, Friedman A, Benninger F. Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study. Epilepsia. 2024 Nov 6. doi: 10.1111/epi.18145.
- Crespo Pimentel B, Kuchukhidze G, Xiao F, Caciagli L, Hoefler J, Rainer L, Kronbichler M, Vollmar C, Duncan JS, Trinka E, Koepp MJ, Wandschneider B. Quantitative MRI Measures and Cognitive Function in People With Drug-Resistant Juvenile Myoclonic Epilepsy. Neurology. 2024 Oct 22;103(8):e209802.
- Crespo Pimentel B, Kuchukhidze G, Xiao F, Caciagli L, Höfler J, Rainer L, Kronbichler M, Vollmar C, Duncan JS, Trinka E, Koepp M, Wandschneider B. Sodium valproate is associated with cortical thinning of disease-specific areas in juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry. 2024 Dec 16;96(1):11-14. doi: 10.1136/jnnp-2024-333703.
- Vorderwülbecke BJ, Wandschneider B, Weber Y, Holtkamp M. Genetic generalized epilepsies in adults - challenging assumptions and dogmas. Nat Rev Neurol. 2022 Feb;18(2):71-83. doi: 10.1038/s41582-021-00583-9. Epub 2021 Nov 26.